OBJECTIVE: The principal objective is to determine if there are characteristic free radical changes that occur during carcinogenesis. APPROACH: A close link between free radicals and carcinogenesis has been postulated and Soviet scientists have published numerous reports supporting this concept. They report that early in carcinogenesis, before there are any other biochemical or histological changes pathognomonic of malignancy, free radicals increase significantly. They further report that drugs that specifically interfere with these free radical increases retard or prevent the malignant changes. On the basis of these results these free radical changes have been proposed as the basis of tests for: 1) early diagnosis of clinical cancer, 2) assessment of the extent of spread of malignant cells and 3) the development of a unique new class of antineoplastic agents. These findings, however, have not been generally accepted by non-Soviet scientists because of lack of familiarity with these experiments, disagreements on the proposed theoretical basis for expecting such free radical changes and lack of agreement of experimental results with those of the involved Soviet scientist. It is proposed that a series of experiments be carried out to test the validity of the hypothesis of an important link between free radicals and carcinogenesis. Several experimental tumor systems will be studied by periodic measurements of free radical and other paramagnetic changes by electron spin resonance (ESR) spectroscopy combined with histological studies of the same specimens. The study will include tumors induced by transplantation, chemical carcinogens and viruses. The relation between chemical modification of free radicals and effects on tumor development will also be examined. The ESR studies will include a thorough examination of the effect of lyophilization on the ESR spectra, because one of the principal sources of criticism of the Soviet results has been their use of this sample preparation technique with its associated artifacts.